Biology subjects

Maruta, N.

Publications and source records attributed to Maruta, N..

5 recordsLinked to original sources

bioRxiv2026

Structural basis of canonical TIR-NLR activation in plant innate immunity

In plants, intracellular NLRs (nucleotide-binding leucine-rich repeat receptors) detect pathogen effector proteins, form oligomeric resistosomes, and activate ETI (effector-triggered immunity). NLRs contain N-terminal signaling, central NB-ARC (nucleotide-binding) and C-terminal LRR (leucine-rich repeat) domains. NLRs with N-terminal TIR (Toll/interleukin-1 receptor) domains (TNLs) hydrolyze NAD+ (nicotinamide adenine dinucleotide) to generate signaling molecules. We determined cryo-EM structures of flax M, a canonical non C-JID (C-terminal jellyroll/Ig-like domain) TNL, in both monomeric autoinhibited conformation, and tetrameric resistosome after activation by its rust fungal effector AvrM-A. AvrM-A homodimers dissociate into monomers to bind directly to the LRR and NB-ARC domains in the M resistosome. The resistosome structure includes a non-hydrolyzable NAD+ analogue, revealing the substrate NAD+ recognition mechanism by the TIR domains. M cleaves NAD+ and generates the same signaling compounds as the related flax TNL, L6. Our findings explain the mechanism of TNL signaling, and provide a basis for rational engineering of disease-resistant crops.

plant biology↗

bioRxiv2025

Natural variation in an NLR pair confers thermostable resistance to a devastating bacterial pathogen

Climate change reshapes host-pathogen interactions by increasing pathogen aggressiveness and weakening plant immune responses, particularly under heat stress. Nucleotide-binding leucine-rich repeat (NLR) immune receptors, key players in pathogen recognition, are altered under elevated temperatures in both plants and mammals, posing a major challenge to disease resistance. In Arabidopsis thaliana, the well-described RPS4/RRS1 NLR pair confers resistance to the worldwide devastating phytopathogenic Ralstonia pseudosolanacearum. Here, by combining the exploration of natural genetic variation with genetic mapping, polymorphism analysis, structural modeling, and functional complementation, we demonstrated that the paucity of full thermostable resistance is primarily associated with a unique RPS4/RRS1 haplotype carrying key substitutions in leucine-rich repeat domains. These findings reveal natural genetic diversity as a source of thermostable resistance, highlighting promising opportunities to engineer climate-resilient plants.

plant biology↗

bioRxiv2025

The Arabidopsis TIRome informs the design of artificial TIR (Toll/interleukin-1 receptor) domain proteins

The TIR (Toll/interleukin-1 receptor) domain is an ancient protein module that functions in immune and cell death responses across the Tree of Life. TIR domains encoded by plants and prokaryotes function as enzymes to produce diverse small molecule immune signals. Plant genomes can encode hundreds of TIR-domain containing proteins - many of which confer important agricultural disease resistance as TIR-NLR (nucleotide-binding, leucine-rich repeat) immune receptors. Despite their importance, how natural variation influences TIR enzymatic output and immunity-associated cell death is largely unexplored. We assayed a complete collection of the TIR domains of Arabidopsis thaliana Col-0 (the "AtTIRome") to explore variation in TIR metabolite production and cell death signaling. Roughly half of the AtTIRome triggered cell death in transient assays. Artificial TIR proteins designed based on consensus sequences of the AtTIRomes cell death phenotypic classes revealed polymorphisms controlling variation in TIR cell death elicitation and metabolite production. Structure-function analyses of artificial TIRs revealed that natural variation in the "BB-loop", a flexible region overlying the catalytic pocket, determines differences in function across Arabidopsis TIR-containing proteins. We further demonstrate that artificial TIRs are functional on an NLR chassis and that BB-loop variation can tune the activity of a natural TIR-NLR protein. These findings shed light on the diversity of TIR outputs and reveal methods to design and engineer TIR-based immune receptors. Significance StatementTIR (Toll/interleukin-1 receptors) domain proteins perform immune signaling across the Tree of Life. TIR domains are enzymes that can process NAD+ to generate diverse small molecule signals. In order to better understand TIR-based signaling, we leveraged Arabidopsis natural variation across [~]150 TIR proteins to inform the design of artificial TIRs, define features that control output, and tune the output of a natural TIR immune receptor. The engineering of plant immune pathways will enable the optimization of disease resistance to safeguard yields.

plant biology↗

bioRxiv2022

Chemical structures of cyclic ADP ribose (cADPR) isomers and the molecular basis of their production and signaling

Cyclic ADP ribose (cADPR) isomers are important signaling molecules produced by bacterial and plant Toll/interleukin-1 receptor (TIR) domains via NAD+ hydrolysis, yet their chemical structures are unknown. We show that v-cADPR (2cADPR) and v2-cADPR (3cADPR) isomers are cyclized by O-glycosidic bond formation between the ribose moieties in ADPR. Structures of v-cADPR (2cADPR)-producing TIR domains reveal that conformational changes are required for the formation of the active assembly that resembles those of Toll-like receptor adaptor TIR domains, and mutagenesis data demonstrate that a conserved tryptophan is essential for cyclization. We show that v2-cADPR (3cADPR) is a potent activator of ThsA effector proteins from Thoeris anti-phage defence systems and is responsible for suppression of plant immunity by the effector HopAM1. Collectively, our results define new enzymatic activities of TIR domains, reveal the molecular basis of cADPR isomer production, and establish v2-cADPR (3cADPR) as an antiviral signaling molecule and an effector-mediated signaling molecule for plant immunity suppression. One-Sentence SummaryThe chemical structures of two O-glycosidic bond-containing cyclic ADP ribose isomers, the molecular basis of their production, and their function in antiviral and plant immunity suppression by bacteria are reported.

biochemistry↗

bioRxiv2021

Self-association configures the NAD+-binding site of plant NLR TIR domains

TIR domains are signalling domains present in plant nucleotide-binding leucine-rich repeat receptors (NLRs), with key roles in plant innate immunity. They are required for the induction of a hypersensitive response (HR) in effector-triggered immunity, but the mechanism by which this occurs is not yet fully understood. It has been recently shown that the TIR domains from several plant NLRs possess NADase activity. The oligomeric structure of TIR-containing NLRs ROQ1 and RPP1 reveals how the TIR domains arrange into an active conformation, but low resolution around the NAD+ binding sites leaves questions unanswered about the molecular mechanisms linking self-association and NADase activity. In this study, a number of crystal structures of the TIR domain from the grapevine NLR RUN1 reveal how self-association and enzymatic activity may be linked. Structural features previously proposed to play roles involve the "AE interface" (mediated by helices A and E), the "BB-loop" (connecting {beta}-strand B and helix B in the structure), and the "BE interface" (mediated by the BB-loop from one TIR and the "DE surface" of another). We demonstrate that self-association through the AE interface induces conformational changes in the NAD+-binding site, shifting the BB-loop away from the catalytic site and allowing NAD+ to access the active site. We propose that an intact "DE surface" is necessary for production of the signalling product (variant cyclic ADPR), as it constitutes part of the active site. Addition of NAD+ or NADP+ is not sufficient to induce self-association, suggesting that NAD+ binding occurs after TIR self-association. Our study identifies a mechanistic link between TIR self-association and NADase activity.

biochemistry↗